This invention relates generally to medical devices and methods, and more particularly, to catheters, systems, kits, and methods for treating cerebral ischemia, such as acute or chronic ischemia associated with stroke.
Stroke remains a devastating and common clinical disorder, yet treatment options are limited. In recent years, the field of cardiology has witnessed remarkable advances in the prevention and treatment of ischemic heart disease. However, cerebral ischemia has eluded the stroke research community's fervent efforts to reverse or even limit the degree of neurologic injury that develops within only minutes or hours of stroke onset yet may result in lifelong disability.
Much attention has been devoted to the ischemic cascade, or sequence of cellular and molecular events that occur in the brain when arterial blood flow is diminished. Traditional descriptions of the ischemic cascade in stroke focus on organ-specific aspects of pathophysiology such as deleterious events in brain tissue, neglecting critical vascular elements such as hemodynamic compensation, endothelial ischemia, or blood-brain barrier permeability that accompany early phases of acute ischemic stroke. Recognition of the neurovascular unit has recently shifted focus to the complex interaction between vascular elements and specific pathophysiologic events in the ischemic brain. Increasing use of advanced noninvasive imaging modalities and endovascular procedures for acute ischemic stroke has also provided a wealth of information regarding the critical role of collateral perfusion.
The emphasis on vascular aspects of acute ischemic stroke prevails in the clinical realm. Almost a dozen years after the introduction of thrombolysis for acute ischemic stroke, the only advance in treatment has been the US Food and Drug Administration (FDA) clearance of the Merci device (Concentric Medical, Mountain View, Calif.) for mechanical thrombectomy. As a result, the only approved means to treat stroke is to remove the clot obstructing an artery feeding the brain with essential oxygen and nutrients. Unfortunately, this approach can only be used in a subset of cases.
Recent investigational strategies have attempted to improve upon this approach with newer and potentially safer clot-busting approaches. Novel thrombolytic and antithrombotic drugs, alternative endovascular thrombectomy devices, and even noninvasive use of ultrasound have been proposed to enhance recanalization. Although recanalization is an important facet of acute stroke therapy, numerous limitations abound. Persistent arterial occlusion occurs in a substantial subset of cases, and recanalization is not tantamount to reperfusion, as distal emboli may ensue. Rethrombosis may occur in one of every three thrombolysis cases. Reperfusion of the proximal artery may also not herald improved neurologic outcome, as some regions of downstream ischemia may not be vulnerable due to established compensation via collateral perfusion. Proximal recanalization may also hasten hemorrhagic transformation or bleeding into areas of severe ischemic injury. Neuroprotective strategies have attempted to circumvent this aspect by conducting clinical trials that consider ischemia and hemorrhage. However, effective delivery of neuroprotective agents is also dependent on collateral perfusion, underscoring the emphasis on vascular pathophysiology.
The introduction of devices to treat acute ischemic stroke has also transformed the field. Endovascular devices for neurointerventional procedures have been proliferating for many years. Debate concerning these techniques has focused on the distinction between clinical outcomes and vascular end points, such as the technical efficacy of arterial recanalization. The dissimilar regulatory processes for approval of drugs and devices have also received much attention. More subtle issues relate to the nature of these different therapeutic approaches. Devices may selectively target specific biophysical mechanisms and thereby enhance an endogenous pathophysiologic process, whereas drugs may exhibit more complex interactions.
Unlike drugs administered in a standard fashion, the efficacy of devices may depend on operator experience, as procedural variables may be difficult to ascertain. Devices have flourished in the growing competition to develop effective therapies for acute ischemic stroke. Current investigational device strategies include infrared laser therapy transmitted through the skull, stimulation of the sphenopalatine ganglion, and endovascular catheters for novel recanalization approaches, induction of hypothermia, and perfusion augmentation.
The concept of blood diversion due to vascular collapse as a mechanism of perifocal cerebral ischemia, and the possibility to abolish this diversion with increased venous pressure, has been previously described. However, this has never been applied to treat patients in whom venous steal is present, where blood, flowing in the path of least resistance, is diverted from areas where it is needed (e.g., in the immediate peristroke vicinity). Moreover, none of the existing methods for treatment of stroke or cerebral ischemia directly address enhancement of penumbral blood flow.